The Strong Heart Study (SHS) is a population-based longitudinal study to investigate cardiovascular disease (CVD) and its risk factors in 13 American Indian communities in 3 geographic areas (Arizona, the Dakotas, and Oklahoma). Data to date show CVD rates in American Indians are now higher than the US average and appear to be increasing. In the SHS Phase I examination, 1,527 eligible tribal members from Oklahoma aged 45 to 74 years were recruited and examined between 1989 and 1991. Phases II and III of SHS were performed in 1993-1995 and in 1997-1999, respectively, to re-examine the original cohort. In Phase III, a highly successful pilot family study was also conducted to demonstrate the feasibility of a genetic study of CVD in American Indians. The Oklahoma center recruited 309 family members of the original cohort from 11 large families to begin the investigation of the genetic determinants of CVD and its risk factors. This application proposes a five-year extension (Phase IV) of SHS to expand the family study and to continue morbidity and mortality surveillance of the original cohort. Each of the 3 field centers will recruit an additional 900 participants who are members of families containing at least 2 SHS cohort members. Furthermore, the pilot study family members will be invited to a follow-up exam after the 900 members are enrolled at each center. The Phase IV family study exams will include cardiac and carotid ultrasound exams, blood pressures, noninvasive measurements of arterial stiffness (tonometry), ECGs, anthropometry, medical history, behavioral assessments (socio-economic status, diet, smoking, alcohol, and physical activity), blood chemistries, lipids, and DNA. The specific aims of the Phase IV study are to expand the family study to increase the power for genetic analyses, to continue surveillance of the original cohort to ascertain more CVD cases, to investigate the association of some pertinent biomarkers and cardiac functions with the development of CVD, and to initiate mortality surveillance in the family members. The Center for American Indian Health Research at the College of Public Health, University of Oklahoma Health Sciences Center proposes to continue its participation in Phase IV of the study as a Field Center and as the Coordinating Center.